It is well known that bis-chromophoric dyes and pigments (e.g. disazo compounds) prepared from unsubstituted or 3,3'-disubstituted benzidines exhibit bathochromic spectral shifts relative to identically substituted mono-chromophoric colorants (e.g. monoazo compounds) prepared from aniline, or 2-substituted derivatives thereof. For example, in two papers by Christie et al. (Dyes Pigm., 9 (1988) 37-56; Dyes Pigm., 11 (1989) 109-121), a diarylide pigment (see, compound 1) exhibited a .lambda..sub.max of 445 nm in N,N-dimethylformamide (abbreviated as DMF) while the corresponding monoarylide pigment (see, compound 2) exhibited a .lambda..sub.max of 392 nm in DMF. ##STR2##
In the case of azo pigments derived from acetoacetanilide, monoarylide pigments (e.g., compound 2) are characterized by good light fastness and poor solvent resistance. Diarylide pigments (e.g., compound 1), however, possess higher color strength, good thermal stability, and enhanced solvent resistance compared to the monoarylide pigments. Thus, diarylide pigments are the preferred class of colorants for many applications.
However, the significant bathochromic shift observed when benzidine-type intermediates are employed in the preparation of diarylide pigments (relative to when aniline-type compounds are used for the synthesis of monoarylide pigments) can limit the color gamut of diarylides. In particular, greenish-yellow dyes and pigments are not easily accessible. Thus, the ability to prepare colorants based on derivatives of benzidine that exhibit hypsochromic shifts to those normally achievable is desirable.
With respect to diarylide and monoarylide pigments, if it is presumed that diarylides exhibit bathochromic shifts relative to analogous monoarylides due to, in the most part, significant .PI. orbital overlap across the biphenyl linkage at the 1,1'-position, where the numbering of the benzidine positions is as follows ##STR3## then, it follows that hypsochromic shifts should be obtainable by decreasing the .PI. orbital overlap.
One method by which a reduction in the degree of .PI. orbital overlap could be achieved is by twisting of the biphenyl group about the 1,1'-bond, for example, by insertion of bulky substituents in the 2,2'-positions. Examination of the open literature (see, for instance, J. Lenoir, The Chemistry of Synthetic Dyes, Volume V, ed. K. Venkataraman, Academic Press, New York (1952) 345) shows that an example of a diarylide pigment containing a substituent other than hydrogen in the 2,2'-positions has been reported. The example is compound 3 (C.I. Pigment Yellow 15). Compound 4 (C.I. Pigment Yellow 81) and compound 5 (C.I. Pigment Yellow 113) are two other examples from the Colour Index (3rd Ed., Lund-Humphries: London, 1971). See Table 1 below for these three structures.
TABLE 1 __________________________________________________________________________ Selected diarylide pigments derived from twisted benzidines 1 STR4## - Compound R.sub.1 R.sub.2 X.sub.1 X.sub.2 X.sub.3 __________________________________________________________________________ 3 OMe Cl Me Me H 4 Cl Cl Me Me H 5 Cl Cl Me Cl H 6 Cl H Me Cl H __________________________________________________________________________
Compounds 3, 4, and 5 are indeed hypsochromic relative to analogous pigments in which the substituent at each position R.sub.2 is hydrogen. For instance, compound 6 (C.I. Pigment Orange 14) is orange, whereas compound 5 is yellow.
Although the inclusion of a bulky substituent into the 2,2'-positions of benzidine-type compounds has been undertaken, thereby providing a hypsochromic shift in the resultant colorant, previously made compounds are believed to be genotoxic, and are therefore potentially hazardous to humans and the environment. By genotoxic is meant these compounds interact with DNA to produce heritable changes in a cell or organism. In humans, such changes are associated with birth defects, carcinogenesis, and other types of diseases.
It is well documented in the open literature that benzidine and certain well-known derivatives of benzidine, for instance, 3,3'-dichlorobenzidine, 3,3'-dimethylbenzidine and 3,3'-dimethoxybenzidine, hereinafter referred to as common benzidines, are mutagenic. It is also known that certain colorants prepared from common benzidines are mutagenic. Furthermore, it is generally believed that compounds that exhibit mutagenic activity are potentially carcinogenic, and that the manufacture and use of such substances presents an occupational risk, as well as a potential risk to the health of living organisms that are exposed to those substances.
Following the discovery of the genotoxicity of benzidine, and later the mutagenicity of common benzidines, legislation was introduced in many countries either banning or severely restricting the industrial production and use of these compounds (see, for instance, OSHA. Carcinogens: Occupational Health and Safety Standards; U.S. Federal Register 39 (1974) 3756-3797, and The Carcinogenic Substances Regulations 1967, U.K. Statutory Instrument No. 879). For a discussion of the genotoxicity of benzidine and its congeners, see, for instance, Clarke (Int. Dyer & Text. Printer, No. 5, 250-255) and Fishbein (The Handbook of Environmental Chemistry, Vol. 3, Part C, Ed. by O. Hutzinger, Springer-Verlag, New York (1984) 1-40).
The restricted synthesis and use of common benzidines has resulted in a large reduction in their employment in the field of coloration, as well as other fields such as polymer cross-linking and clinical analysis. Production of high volume dyes based on benzidine itself and its congeners has been practically discontinued in the Western World.
In certain countries, however, the use of pigments derived from common benzidines is permitted, since pigments tend to be unchanged during normal processing conditions, and since prolonged exposure of living organisms to pigments derived from common benzidines has not been shown to result in significant genotoxicity. Hence, pigments derived from common benzidines, particularly 3,3'-dichlorobenzidine, are still available commercially. In fact, diarylide pigments derived from 3,3'-dichlorobenzidine command the major market share of organic yellow pigments.
Nevertheless, the occupational risk remains for manufacturing common benzidines themselves prior to their conversion into pigments. There is a risk also of small amounts of common benzidines in their unconverted form becoming incorporated into pigments, and therefore being released into receiving waters following pigment processing. Furthermore, there is a risk of common benzidines being released upon thermal degradation of pigments derived from common benzidines following certain processing conditions, such as melt extrusion of pigment-colored polymers.
An examination of the pertinent literature prior to the discovery of the genotoxicity of benzidine reveals the commercial importance of dyes and pigments prepared from common benzidines. Approximately 250 colorants derived from benzidine, approximately 90 colorants derived from 3,3'-dimethoxybenzidine (o-dianisidine), and approximately 95 colorants derived from 3,3'-dimethylbenzidine (o-tolidine) are listed in the Colour Index (3rd Ed., Lund-Humphries: London, 1971). The commercial importance of common benzidines was due in part to the economy and ease with which such compounds could be produced, and also to the desirable technical properties the aforementioned compounds can impart to a colorant.
In view of the commercial importance of common benzidines prior to the discovery of their harmful effects to living organisms, the prospect remains that production of such compounds could be restored to the marketplace on a wider scale should a method be found that significantly reduces the harmful effects of benzidine-type compounds. In recent years, researchers have worked towards the development of nonmutagenic amines, since mutagenicity is correlated with carcinogenicity. In addition, in vitro test methods have been developed to assess the mutagenic activity of compounds as a means of predicting carcinogenicity.
The most widely accepted mutagenicity screening test procedure for amines is the Salmonella mammalian microsome mutagenicity assay developed by Ames et al. (Mutat. Res., 31 (1975) 347), hereinafter referred to as the Ames test. Subsequently, a modification of the Ames test was introduced by Prival et al. (Mutat. Res., 97 (2) (1982) 103) specifically for evaluating the mutagenicity of azo compounds, hereinafter referred to as the Prival modification. For a general discussion of mutagenicity as it pertains to colored materials, see, for instance, Freeman et al., Genotoxicity of Azo Dyes: Bases and Implications, Physico-Chemical Principles of Color Chemistry, Advances in Color Chemistry Series, Vol. 4, ed. by A. T. Peters and H. S. Freeman (Blackie Academic Press: Glasgow, 1996) 254-291; Freeman et al., Dyes Pigm. 8 (6) (1987) 431-47; and Freeman et al., CHEMTECH, July (1991), 438-445.
The discovery by Shahin et al. (Mutation. Res. 79 (1980) 289; Environ. Mutagen. 7 (4) (1985) 535) that the mutagenicity of aromatic amines can be lowered or removed by incorporating bulky alkyl or alkoxy substituents ortho to the amino group on a molecule has spurred significant interest in this area, particularly for a method to prepare nonmutagenic derivatives of benzidine.
In one patent, DE 3 511 544 A1 to Hunger et al., described is the synthesis of nonmutagenic derivatives of benzidine of the following formula ##STR5## wherein R represents n-butyl, isopentyl, or phenyl. These compounds were reported to be nonmutagenic in the Ames test, presumably due to the ability of bulky substituents in the two ortho positions to the two amino groups in the 4,4'-positions to prevent metabolic activation.
In another patent, DE 3 511 545 A1 to Hunger et al., described is the synthesis of derivatives of benzidine of the following formula ##STR6## wherein R represents n-propyl, isopropyl, n-butyl, isobutyl, 1-methylpropyl, n-propoxy, isopropoxy, isobutoxy, 1-methylpropoxy, or 2-methoxyethoxy. These compounds were reported to be nonmutagenic in the Ames test.
In a later patent, DE 3 534 634 A1 to Bauer et al., nonmutagenic compounds of the type described by Hunger et al. were used as intermediates for the synthesis of water soluble disazo dyes of the following formula ##STR7## wherein R represents groups as described in the two patents to Hunger et al., and B and B' represent, for instance, substituted naphthalene groups of the following formula ##STR8## wherein X represents, for instance, OH, or NH.sub.2, and n represents 0, 1, or 2.
Furthermore, utilization of a nonmutagenic derivative of benzidine is described in Holland et al. (Tetrahedron, 30, No. 18 (1974) 3299-3302) and also in U.S. Pat. No. 4,211,845 to Conshaw et al. In both instances, a benzidine derivative of the following formula ##STR9## is employed as a reagent for detecting the presence of, for example, glucose in fluids. The compound, 3,5,3',5'-tetramethylbenzidine, is nonmutagenic in the Ames test.
A different approach that has been taken to reduce the occupational risk of colorants derived from benzidines involves the preparation of dyestuff intermediates that provide technical properties similar to the common benzidines, while exhibiting low genotoxicity. An example of this approach is shown in U.S. Pat. No. 5,180,817 to Ogino et al., which discloses compounds having, for instance, the following formula ##STR10## as replacements for benzidine.
Despite the aforementioned methods for the generation of nonmutagenic derivatives of benzidine, examination of the open literature shows that benzidine-type compounds have not been disclosed that contain bulky alkyl, alkoxy, aryloxy, and/or halogeno substituents ortho to the amino functional groups and substituents ortho to the biphenyl linkage, the former providing nongenotoxicity and the latter also providing colorants giving hypsochromic shifts.